Mycophenolate Mofetil

Evidence Level: L3

Predicted Indications: 10

Mycophenolate Mofetil
Mycophenolate Mofetil: From Transplant Immunosuppression to HIV Infectious Disease

## Pharmacist Assessment Report

Mycophenolate Mofetil: From Transplant Immunosuppression to HIV Infectious Disease

One-Sentence Summary

Mycophenolate mofetil (MMF) is an immunosuppressant that is generally used to prevent organ transplant rejection. The SAHPRA registration record supplied does not state its approved indication. The TxGNN model predicts it may be effective for HIV infectious disease. The search retrieved 10 clinical trials and 20 publications, but only a few are directly relevant, and there is no completed Phase 3 confirmation.

Quick Overview

Item	Content
Original Indication	Not stated in the SAHPRA registration record (MMF is generally an immunosuppressant used in transplantation)
Predicted New Indication	HIV infectious disease
TxGNN Prediction Score	99.86%
Evidence Level	L3
South Africa Market Status	Marketed
Number of SAHPRA Registrations	1
Recommended Decision	Hold

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available in the source record. Based on the assessment in the evidence pack, the active metabolite, mycophenolic acid, inhibits the enzyme IMPDH. This depletes guanosine nucleotides and limits lymphocyte proliferation.

In HIV, chronic immune activation is linked to CD4 T-cell depletion and disease progression. Fewer activated CD4+ T cells could mean fewer cells to support viral replication. Depleting intracellular deoxyguanosine triphosphate (dGTP) may also boost the activity of guanosine-analogue antiretrovirals such as abacavir and didanosine. Laboratory and small clinical studies have explored this idea.

The mechanism is plausible but double-edged. Immunosuppression in a person with HIV carries a risk of opportunistic infection. The available Phase 4 trials, pilot studies and pharmacokinetic studies mainly provide safety and PK information. None shows an established virological or clinical benefit.

Clinical Trial Evidence

Ten trials were retrieved. The table lists the five most relevant, plus three that give only indirect information. The other two, NCT06869265 (a haploidentical transplant conditioning study in acute myeloid leukaemia) and NCT01288131 (anti-EPO pure red cell aplasia), are off-target and omitted. Trials NCT02793544 and NCT01288131 and other transplant or conditioning studies are also off-target for HIV. No SANCTR or PACTR identifiers were found in the pack.

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00120419	Phase 4	Unknown	90	MAN2 study: MMF in antiretroviral-naive, chronically HIV-1-infected patients. It tests whether MMF reduces immune hyperactivation and slows CD4 decline. No results shown.
NCT00247494	Phase 4	Unknown	90	MAN2 substudy: MMF 500 mg twice daily vs untreated control, looking at cardiovascular surrogate markers. Not an HIV control endpoint.
NCT00021489	Phase 2	Withdrawn	0	MMF added to abacavir in treatment-experienced patients, to assess safety and viral load. Withdrawn with no participants, so it yields no evidence.
NCT00038272	Phase 2	Completed	56	Placebo-controlled study of DAPD (amdoxovir) alone vs DAPD plus MMF in treatment-experienced HIV. MMF is an add-on arm and the primary drug under test is DAPD.
NCT00009009	Phase 2	Completed	10	Kidney transplantation in HIV-positive patients with end-stage renal disease. MMF is probably part of the immunosuppressive regimen, so it gives indirect safety data.
NCT00112593	NA	Completed	5	Stem cell transplant to induce mixed chimerism in HIV-infected patients. MMF is post-transplant immunosuppression rather than the tested intervention.
NCT01453192	Phase 3	Completed	27	Kidney transplant follow-up in HIV-1-infected patients on a raltegravir regimen. No clear MMF-in-HIV link, so it is not counted as Phase 3 evidence for MMF.

Literature Evidence

Twenty publications were retrieved. The ten most relevant are listed. Study types follow the pack’s classification where available.

PMID	Year	Type	Journal	Key Findings
15353978	2004	Clinical study	AIDS	HAART with or without MMF in treatment-naive patients, looking at the decay rate of plasma HIV-1 RNA and the latent cellular reservoir. The abstract excerpt does not report results.
15213566	2004	Randomized pilot	J Acquir Immune Defic Syndr	17 patients were randomized to MMF or continued HAART, then HAART was stopped, to assess immune response and viral load.
12352149	2002	Clinical study	J Acquir Immune Defic Syndr	MMF 500 mg twice daily added to abacavir-containing regimens in 5 patients failing therapy. The title reports dGTP depletion and a decrease in plasma HIV-1 RNA.
11391161	2001	Pilot study	J Acquir Immune Defic Syndr	Seven patients with AIDS and multidrug-resistant HIV received MMF, abacavir, didanosine, amprenavir and ritonavir. Therapy was well tolerated.
17885292	2007	Clinical study	AIDS	Safety, tolerability and antiretroviral activity of DAPD with or without MMF in drug-resistant HIV.
16379601	2005	Clinical study	AIDS Res Hum Retroviruses	Studied whether MMF plus HAART harms T-cell proliferation and lymphocyte reconstitution in treatment-naive acute and chronic HIV. The title reports no detrimental immunological effects.
15871638	2005	PK-PD study	Clin Pharmacokinet	Pharmacokinetics and pharmacodynamics of low-dose MMF in patients on abacavir, efavirenz and nelfinavir. Monitoring is recommended because of the low doses.
15355127	2004	PK interaction study	Clin Pharmacokinet	Effect of MMF on antiretroviral pharmacokinetics and on intracellular dCTP, dGTP and lamivudine-triphosphate pools.
17017956	2006	Review	Curr Top Med Chem	Reviews the rationale for immunosuppressive drugs in HIV disease, targeting chronic immune activation and host T-cell signalling.
39396546	2025	Case report	Trop Doct	Complete renal response of IgA vasculitis to steroid plus MMF in an adult with HIV. This concerns a complication of HIV, not HIV itself.

South Africa Market Information

Registration Number	Product Name	Dosage Form	Approved Indication
Reg. No. 41/34/0815	Mycocept	Capsule (oral)	Not stated in the registration record

Safety Considerations

Please refer to the SAHPRA-approved Professional Information (PI) for safety information. Report adverse drug reactions to SAHPRA.

The one safety point from the evidence assessment is that immunosuppression in people with HIV carries a risk of opportunistic infection.

Conclusion and Next Steps

Decision: Hold

Rationale: The mechanism is plausible, and small pilot and PK studies exist. However, there is no completed Phase 3 trial, no established virological or clinical benefit, and a real infection risk in an already immunocompromised population. The safety information from the SAHPRA package insert is also missing, so safety screening cannot proceed.

To proceed, the following is needed:

The SAHPRA Professional Information (warnings, contraindications, interactions), to allow safety screening
Confirmation of the approved indication for Mycocept (Reg. No. 41/34/0815)
Mechanism of action data from DrugBank
Results from the MAN2 trials (NCT00120419, NCT00247494), whose status is unknown
A controlled trial with virological and clinical endpoints, with a safety monitoring plan for opportunistic infections
Route compatibility assessment, which is still pending

Among the other predictions, only multiple sclerosis also reached L3. There, one small early-phase trial tests MMF directly, as an add-on to interferon beta-1a (NCT00618527). The remaining predictions (ranks 2–5 and 7–10) have no clinical evidence retrieved and are best treated as graph artefacts or preclinical-only leads.

This report is for research reference only and does not constitute medical advice. Predicted indications require clinical validation before any use.

Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.